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Patients were randomly assigned to either the high-dose methotrexate arm or the control arm.[4] In the POG-9404 study, patients were also randomly assigned to receive doxorubicin with or without dexrazoxane to determine the efficacy of dexrazoxane in preventing late cardiac mortality.[7][Level of evidence B1] There was no difference in EFS between patients with T-ALL who were treated with dexrazoxane and patients who were not treated with dexrazoxane (cumulative doxorubicin dose, 360 mg/m2).[7] The frequency of grade 3 and grade 4 toxicities that occurred during therapy was similar between the randomized groups, and there was no difference in cumulative incidence of second malignant neoplasms

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7) and induced ERK-CREB signaling activation, contributing to both Gcg and Vgf upregulation (Supplementary Fig

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